Effects of trisodium nitrilotriacetate monohydrate, nitrilotriacetic acid and ammonium chloride on urinary bladder carcinogenesis in rats pretreated with N-bis(2-hydroxypropyl) nitrosamine

Abstract

The effects of trisodium nitrilotriacetate monohydrate (Na 3 NTA · H 2O) nitrilotriacetic acid (H 3NTA) and ammonium chloride (NH 4Cl) on two-stage urinary bladder carcinogenesis were examined. Carcinogenesis was initiated by administration of 0.2% N-bis (2-hydroxypropyl)-nitrosamine (DHPN) to male Wistar rats in the drinking water for 2 weeks, and then the animals were treated with basal diet containing Na 3NTA · H 2O, Na 3NTA · H 2O plus NH 4Cl, H 3NTA, H 3NTA plus NH 4Cl, or without these chemicals for 28 weeks. Na 3NTA · H 2O increased significantly the resultant incidence of neoplastic and preneoplastic lesions of the urinary bladder. Moreover, treatment with Na 3NTA · H 2O, without the initation, itself induced papillary or nodular (PN)-hyperplasia. H 3NTA produced only a slight increase in the incidence of preneoplastic urinary bladder lesions (PN-hyperplasia) in rats initiated by DHPN, and this was not statistically significant. Elevation of both pH and sodium ion concentration in the urine were correlated with promotion of tumor development. These data showed that Na 3NTA · H 2O was more effective than H 3NTA with regard to promoting potential, and that changes in both urinary pH and concentration of sodium played important roles in enhancement of urinary bladder tumorigenesis by these chemicals.